The use of a sliding lid for immobilized droplet extraction technology provides a simple approach to sample preparation. The technology contemplates a lower microtiter plate with a plurality of wells for receiving biological samples therein. An upper plate has a lower surface directed to the upper surface of the microliter plate. A force is positioned adjacent the upper plate and attracts target bound solid phase substrate in the biological sample toward the lower surface of the upper plate. The upper plate is movable from a first position wherein the target bound solid phase substrate in the biological samples are drawn to the lower surface of the upper plate and a second position wherein the target bound solid phase substrate are isolated from the biological samples.
The technology is enabled through the use of a hydrophobic lower surface of the upper plate in combination with the convex menisci of the biological samples in the plurality of wells in microtiter plate, which facilitate fluidic contact with the lower surface of the upper plate. Heretofore, to achieve the convex menisci, the wells of the microtiter plate must be accurately filled. However, such process has certain limitations. First, the stability of a convex droplet is low, as compared to a concave meniscus, making the droplets prone to spilling over the edges of the wells of the microtiter plate. The issue of spillage is exacerbated with fluids having low surface tension (e.g., lysis buffers, ethanol based solutions, detergents). As a result, the microtiter plate may be difficult to move or transport after the wells of the microtiter plates have been filled, thereby hindering the advanced preparation of plates and the disposing of plates without spillage. Second, convex droplets are difficult and/or impractical to prepackage, in part due to the aforementioned limitations. Hence, reagents must be packaged in separate containers, and thereafter, transferred to the wells of the microtiter plate. This, in turn adds steps and complexity to the process. As such, it is highly desirable to provide a mechanism which allows for the reagents/biological samples to remain concave until ready for use. Such a mechanism would enable the reagents/biological samples to be prepackaged on-chip, would simplify user protocols, and would assure that the reagents/biological samples remain in the wells of the microtiter plate so as to allow a user to manipulate the microtiter plate without the fear of spillage of the reagents/biological samples.
Therefore, it is a primary object and feature of the present invention to provide a deformable well for a microtiter plate wherein deformation of the well converts the meniscus of the sample in the well from concave to convex.
It is a further object and feature of the present invention to provide a deformable well for a microtiter plate which allows for reagents/biological samples to be prepackaged therein.
It is a still further object and feature of the present invention to provide a deformable well for a microtiter plate which allows for a user to manipulate the microliter plate without the fear of spillage of the reagents/biological samples prepackaged therein.
It is a still a further object and feature of the present invention to provide a deformable well for a microtiter plate which is simple to use and inexpensive to manufacture.
In accordance with the present invention, a deformable well structure for a microtiter plate is provided. The well structure includes a sample container defining a well for receiving a sample therein. The sample received in the well, has a concave meniscus. A deformation tool is engageable with the sample container and is moveable between a first disengaged position wherein the deformation tool is spaced from the sample container and, a second engaged position wherein the deformation tool engages and deforms at least a portion of the sample container such that the meniscus of the sample in the well is converted from concave to convex.
The sample container includes a generally tubular wall having a first end defining an opening in communication with the well and a second end; and a generally flat wall closing the second end of the tubular wall. The tubular wall may be fabricated from a shape-memory polymer. It is further contemplated for the tubular wall to include a circumferentially extending bellows section formed therein. The bellows section is defined by a plurality of axially compressible pleats formed in the tubular wall.
The deformation tool may include a support bar having a recess. The recess is adapted for receiving the sample container therein. The sample container has a first cross-sectional dimension and the recess in the support bar is defined by first and second spaced sidewalls. The first and second sidewalls defining the recess in the support bar are spaced by a distance less than the cross-sectional dimension of the sample container.
In accordance with a further aspect of the present invention, a deformable well structure for a microliter plate is provided for receiving, a sample fluid therein. The deformable well structure includes a generally tubular wall having an inner surface, a first end defining an opening in communication with the well and a second end. An end wall closes the second end of the tubular wall and has an inner surface. The inner surface of the tubular wall and the inner surface of the end wall defines a well for receiving the sample fluid therein. The sample fluid received in the well has a concave meniscus. Deformation of the tubular wall converts the meniscus of the sample fluid in the well from concave to convex.
The tubular wall may be fabricated from a shape-memory polymer or include a circumferentially extending bellows section formed therein. The bellows section is defined by a plurality of axially compressible pleats formed in the tubular wall. A deformation tool may be engageable with the sample container and is configured to deform the tubular wall. The deformation tool is moveable between a first disengaged position wherein the deformation tool is spaced from the tubular wall and a second engaged position wherein the deformation tool engages and deforms the tubular wall. The deformation tool may include a support bar having first and second spaced sidewalls defining a recess therebetween. The first and second spaced sidewalls are adapted to engage and to deform the tubular wall received in the recess.
In accordance with a still further aspect of the present invention, a method of converting the meniscus of a sample fluid received in a well from concave to convex is provided. The method includes the step of filling a sample container defining the well with the sample fluid. The sample container includes a generally tubular wall having a first end defining an opening in communication with the well and a second end. An end wall closes the second end of the tubular wall. The tubular wall is deformed so as to convert the meniscus of the sample fluid in the well from concave to convex.
Tubular wall may be fabricated from a shape-memory polymer. A circumferentially extending bellows section may be fabricated in the tubular wall. The bellows section is defined by a plurality of axially compressible pleats. The tubular wall may be engaged with a deformation tool. The deformation tool configured to deform the tubular wall upon contact. The deformation tool may include a support bar having first and second spaced sidewalls defining a recess therebetween. The first and second spaced sidewalls are adapted to engage and to deform the tubular wall received in the recess.